Genetic variation in the presynaptic norepinephrine transporter is associated with blood pressure responses to exercise in healthy humans

Utkarsh Kohli, Maureen K. Hahn, Brett A. English, Gbenga G. Sofowora, Mordechai Muszkat, Chun Li, Randy D. Blakely, C. Michael Stein, Daniel Kurnik*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Background The presynaptic norepinephrine transporter (NET) mediates synaptic clearance and recycling of norepinephrine. NET-deficient transgenic mice have elevated blood pressure (BP), heart rate, and catecholamine concentrations. However, the in-vivo effects of common NET variants on cardiovascular regulation at rest and during exercise are unknown. Methods We studied cardiovascular responses and plasma catecholamine concentrations at rest and during bicycle exercise at increasing workloads (25, 50, and 75 W) in 145 healthy participants. We used multiple linear regressions to analyze the effect of common, purportedly functional polymorphisms in NET (rs2242446 and rs28386840) on cardiovascular measures. Results 44 and 58.9% of participants carried at least one variant allele for NET T-182C and A-3081T, respectively. Systolic BP during exercise and systolic BP-area under the curve were higher in carriers of variant NET alleles (P = 0.003 and 0.009 for T-182C and A-3081T, respectively) and NET haplotype -182C/-3081T compared with -182T/-3081A (all P <0.01). Diastolic BP during exercise was also higher at lower, but not at higher exercise stages in carriers of NET -182C (P < 0.01) and -3081T variants (P <0.05). NET genotypes were not associated with catecholamine concentrations or heart rate. Conclusion Common genetic NET variants (-182C and -3081T) are associated with greater BP response to exercise in humans. Pharmacogenetics and Genomics 21:171-178.

Original languageAmerican English
Pages (from-to)171-178
Number of pages8
JournalPharmacogenetics and Genomics
Volume21
Issue number4
DOIs
StatePublished - Apr 2011
Externally publishedYes

Keywords

  • Blood pressure
  • Exercise
  • Norepinephrine t.ransporter.
  • Polymorphism

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